The recent description of immunoregulatory molecules, HLA-DR or Ia, on the surface of gut epithelial cells has raised questions as to their function and possible roles in normal antigen processing and oral tolerance. In order to address these questions, this proposal seeks to characterize the Ia molecules on isolated epithelial cells, or available epithelial cell lines, in terms of their localization (by tissue stains), definition of factors affecting their expression (effects of inflammatory diseases, direct local immunizaaiton and -IFN), comparison with Ia molecules present on ooter antigen presenting cells (by immunoprecipitation or staining with anti DR and anti DS monoclonal antibodies) and comparison of the immune response generated with epithelial cells and mononuclear adherent cells as accessory cells (antigen specific and nonspecific) T cells stimulated by epithelial cells, with or without soluble antigen, will be assessed for suppression and/or cytotoxicity in both antigen specific and nonspecific systems. Findings in the normal state can be compared and contrasted with those in various disease states (inflammatory bowel disease, celiac sprue, etc.) where defects in antigen processing might be present. In this manner one can define "normal" antigen processing in the GI tract, characterize potential abnormalities and, potentially, define mechanisms for the induction of oral tolerance.